The significance of meeting Dawes-Redman criteria in computerised antenatal fetal heart rate assessment.

OBJECTIVE: To investigate the significance of not meeting Dawes-Redman criteria on computerised cardiotocography in high-risk pregnancies. DESIGN: Retrospective observational study. SETTING: UK university hospital. POPULATION: High-risk pregnancies undergoing antenatal assessment. METHODS: We interrogated the database for records of computerised fetal heart rate assessment and pregnancy outcomes. MAIN OUTCOME MEASURES: Neonatal outcome and stillbirths. RESULTS: Excluding duplicate assessment in the same pregnancy, 14 025 records with complete information on the criteria of normality having been met and the outcome of the pregnancy were available. Criteria were not met for 907 records (6.46%). The gestational age of assessment was lower in the group not meeting criteria of normality. Overall, 32 stillbirths occurred in normally formed fetuses (2.28/1000). Stillbirths were more frequent in the group not meeting criteria (odds ratio [OR] 8.78, 95% CI 4.28-18.02). This finding persisted even after records with abnormally low short-term variation (STV) were excluded. The confidence intervals around the rate of stillbirth in the two groups overlapped beyond an STV of 8 ms. CONCLUSIONS: Approximately 1:16 pregnancies do not meet the criteria of normality. The criteria are not met more often at preterm gestation than at term. The risk of stillbirth was higher in the group not meeting criteria of normality, even if cases with low STV are excluded. Cases not meeting criteria should be followed up closely, unless the STV is ≥8 ms. Stillbirths still occurred in the group meeting criteria, but the rate was lower than in the general population.

Nifedipine disturbs fetal cardiac function during hypoxemia in a chronic sheep model at near term gestation.

BACKGROUND: Nifedipine is a widely used drug in pregnancies complicated by maternal hypertensive disorders that can be associated with placental insufficiency and fetal hypoxemia. The evidence regarding fetal myocardial responses to nifedipine in hypoxemia is limited. OBJECTIVE: We hypothesized that nifedipine would not impair fetal sheep cardiac function under hypoxemic environment. In particular, we investigated the effects of nifedipine on fetal ventricular functional parameters and cardiac output. STUDY DESIGN: A total of 21 chronically instrumented fetal sheep at 122 to 134 gestational days (term, 145 days) were included in this study. Fetal cardiac function was evaluated by measuring global longitudinal strain, indices describing ventricular systolic and diastolic function, and cardiac outputs using two-dimensional speckle tracking and tissue and spectral pulsed-wave Doppler echocardiography. Fetal carotid artery blood pressure and blood gas values were invasively monitored. After baseline data collection, fetal hypoxemia was induced by maternal hyperoxygenation. After hypoxemia phase data collection, 9 fetuses received nifedipine infusion, and 12 fetuses received saline infusion. Data were collected 30 and 120 minutes after the infusion was started. After 120 minutes of data collection, maternal and fetal oxygenation were normalized, and normoxemia phase data were collected, while infusion was continued. RESULTS: Hypoxemia decreased fetal carotid artery mean arterial pressure from 40 (8) mm Hg to 35 (8) mm Hg (P<.007), and left ventricular global longitudinal strain showed less deformation than at baseline (P=.001). Under hypoxemia, nifedipine caused a reduction in right ventricular global longitudinal strain (P<.05), a decrease in right ventricular isovolumic relaxation velocity and its deceleration (P<.01) indicating diastolic dysfunction, and a drop in right ventricular cardiac output (P<.05). Nifedipine did not alter fetal left ventricular functional parameters or cardiac output. When normoxemia was restored, fetal right ventricular functional parameters and cardiac output returned to baseline level. CONCLUSION: In hypoxemic fetus, nifedipine impaired right ventricular function and reduced its cardiac output. The detrimental effects of nifedipine on fetal right ventricular function were abolished, when normoxemia was restored. Our findings suggest that in a hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.

Special Report of the Society for Maternal-Fetal Medicine Placenta Accreta Spectrum Ultrasound Marker Task Force: Consensus on definition of markers and approach to the ultrasound examination in pregnancies at risk for placenta accreta spectrum.

Placenta accreta spectrum includes the full range of abnormal placental attachment to the uterus or other structures, encompassing placenta accreta, placenta increta, placenta percreta, morbidly adherent placenta, and invasive placentation. The incidence of placenta accreta spectrum has increased in recent years, largely driven by increasing rates of cesarean delivery. Prenatal detection of placenta accreta spectrum is primarily made by ultrasound and is important to reduce maternal morbidity associated with the condition. Despite a large body of research on various placenta accreta spectrum ultrasound markers and their screening performance, inconsistencies in the literature persist. In response to the need for standardizing the definitions of placenta accreta spectrum markers and the approach to the ultrasound examination, the Society for Maternal-Fetal Medicine convened a task force with representatives from the American Institute of Ultrasound in Medicine, the American College of Obstetricians and Gynecologists, the American College of Radiology, the International Society of Ultrasound in Obstetrics and Gynecology, the Society for Radiologists in Ultrasound, the American Registry for Diagnostic Medical Sonography, and the Gottesfeld-Hohler Memorial Ultrasound Foundation. The goals of the task force were to assess placenta accreta spectrum sonographic markers on the basis of available data and expert consensus, provide a standardized approach to the prenatal ultrasound evaluation of the uterus and placenta in pregnancies at risk of placenta accreta spectrum, and identify research gaps in the field. This manuscript provides information on the Placenta Accreta Spectrum Task Force process and findings.

Perinatal outcomes of twin pregnancies affected by early twin-twin transfusion syndrome: A systematic review and meta-analysis.

INTRODUCTION: Twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet. MATERIAL AND METHODS: This is a systematic review and meta-analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random-effect meta-analyses of proportions were used to analyse the data. RESULTS: Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9-17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6-45.5) in twins managed expectantly, 32.4% (95% CI 16.5-50.7) in those who received laser treatment and 12.5% (95% CI 4.8-23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2-49.8) in twins managed expectantly, 24.7% (95% CI 0.5-80.3) in those who received laser and 20.2 (95% CI 5.8-43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9-87.7) in twins managed expectantly, 47.3% (95% CI 21.4-70.0) in those treated with laser and 28.5% in those who had amnioreduction. CONCLUSIONS: Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.

A survey of current clinical practice of chorionic villus sampling.

OBJECTIVE: The number of invasive procedures (chorionic villus sampling (CVS) or amniocentesis) for fetal testing is decreasing because of the availability of non-invasive prenatal test (NIPT) leading to a centralisation of prenatal diagnostic services to accredited fetal medicine centres. A new survey was conducted 10 years after the previous one to update the current clinical practice among clinicians who regularly perform CVS. METHOD: Consultants from 32 centres in the United Kingdom were invited to take part in an online survey evaluating: The total number of CVS procedures carried out in the unit in a typical week, the preferred route (transabdominal [TA] vs transcervical [TC]), technique (use of local anaesthetic [LA] and needle technique). RESULTS: Response rate was 96.9%; TA was the preferred route (96.8%) in all centres except one. Single-needle technique is used exclusively in half the centres (51.6%). LA is used by most operators (90.3%) before the procedure. Three centres did not routinely use LA for CVS. CONCLUSIONS: Operators across the United Kingdom almost exclusively use the TA route for CVS with single-needle technique in 51.6% of cases. The use of LA prior to CVS is a very common practice in the United Kingdom.

Lower uterine segment placental thickness in women with abnormally invasive placenta.

INTRODUCTION: Ultrasound signs of abnormal placental invasion are subjective in nature. We tested the hypothesis that placental thickness in the lower uterine segment is increased when there is abnormally invasive placenta (AIP) in women with a low-lying placenta. MATERIAL AND METHODS: Retrospective analysis of data of placental thickness in women with ultrasound evidence of major placenta previa or a low-lying anterior placenta was done. The diagnosis of AIP was confirmed both intraoperatively and on histopathology for those managed by partial myometrial excision with uterine conservation or by hysterectomy. RESULTS: In all, 131 records were available for analysis after exclusion of 33 cases due to unsuitable images and eight cases without pregnancy outcomes. The diagnosis of AIP was confirmed in 28 (21.4%) of the 131 cases. The lower segment placental thickness was significantly higher in women with AIP (median = 50.3 mm, IQR: 42.7-64.3) than in those with normal placentation (median = 30.9 mm, IQR: 22.9-42.2, P < 0.001). Logistic regression analysis showed that previous cesarean section and placental thickness on ultrasound were independent predictors for AIP. CONCLUSIONS: Lower uterine segment placental thickness is increased in women with AIP compared with those with noninvasive placentation. This association constitutes a pragmatic objective sign and may be of clinical value in improving prenatal detection of AIP in women with placental implantation in the lower uterine segment. Prospective studies are necessary to ascertain lower segment placental thickness as a predictor for AIP.

Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial.

BACKGROUND: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. OBJECTIVE: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. STUDY DESIGN: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. RESULTS: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). CONCLUSION: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses.

The value of angiogenetic biomarkers in the detection of early onset fetal growth restriction.

OBJECTIVE: The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors. STUDY DESIGN: This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age. RESULTS: 72 pregnancies with SGA were first evaluated at median (IQR) of 28+5 (26+2 -31+3) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR: 0.07-0.36 vs 0.32, 95 % IQR: 0.20-0.53, p = 0.008) and 0.26, 95 % CI: 0.16-0.55 vs 0.43, 95 % IQR: 0.23-0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR: 1.80-7.30 vs 1.74, 95 % IQR:1.11-3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR: 0.27-3.07 vs 0.17, 95 % IQR: 0.08-0.43, p = 0.022). CONCLUSION: These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR.

One-step conservative surgery vs hysterectomy for placenta accreta spectrum: a feasibility randomized controlled trial.

BACKGROUND: Placenta accreta spectrum is a serious condition associated with significant maternal morbidity and even mortality. The recommended treatment is hysterectomy. An alternative is 1-step conservative surgery, which involves the en bloc resection of the myometrium affected by placenta accreta spectrum along with the placenta, followed by uterine reconstruction. Currently, there are no studies comparing the 2 techniques in the setting of a randomized controlled trial. OBJECTIVE: We performed a prospectively registered multicenter randomized controlled trial comparing hysterectomy with 1-step conservative surgery. The aim was to collect feasibility and clinical outcomes of the 2 techniques in women assigned to hysterectomy or 1-step conservative surgery. In addition to assessing participants' willingness to be randomized, we also collected data on intraoperative blood loss, transfusion requirement, serious adverse event, and other clinical outcomes. STUDY DESIGN: Sixty women with strong antenatal suspicion of placenta accreta spectrum were assigned randomly to either hysterectomy (n=31) or 1-step conservative surgery (n=29). RESULTS: During a 20-month period, 60 of the 64 eligible patients (93.7%) underwent randomization. Intention-to-treat analysis showed that the clinical outcomes for 1-step conservative surgery were comparable to those of hysterectomy (median intraoperative blood loss, 1740 mL [interquartile range, 1010-2410] vs 1500 mL [interquartile range, 1122-2753]; odds ratio, 1 [1-1]; P=.942; median duration of surgery, 135 minutes [interquartile range, 111-180] vs 155 minutes [interquartile range, 120-185]; odds ratio, 0.99 [0.98-1]; P=.151; transfusion rate, 58.6% vs 61.3%; odds ratio, 0.96 [0.83-1.76]; P=.768; and adverse event rate, 17.2% vs 9.7%; odds ratio, 1.77 [0.43-10.19]; P=.398; respectively). In the subgroup of women with type 1 class on topographic classification, all participants allocated to 1-step surgery had successful outcomes, which were superior to those of hysterectomy. This was evidenced by the shorter surgery duration (median, 125 [interquartile range, 98-128] vs 180 [129-226] minutes; P=.002), lower transfusion rates (46.2% vs 82.4%), and fewer units of red blood cells transfused (median, 1 [interquartile range, 1-1.8] vs 3 [interquartile range, 2-4] units; P=.007). CONCLUSION: A randomized controlled trial comparing 2 surgical techniques for the treatment of placenta accreta spectrum is feasible. One-step conservative repair is a valid alternative to hysterectomy in the large majority of cases, but this can only be ascertained following intraoperative surgical staging. El resumen está disponible en Español al final del artículo.

Routine screening for placenta accreta spectrum.

Screening for clinically significant placenta accreta spectrum (PAS) is possible with a high degree of accuracy (both sensitivity and specificity >90-95%). The group of women to focus on are those with placenta previa and one or more prior Cesarean deliveries. Screening for PAS not associated with placenta previa is not as productive, and several false negatives have been described. The results of the screening program indicate that women have a low or high probability of PAS. Screen-positive women or those with uncertain ultrasound features should be referred to a center of excellence. Those confirmed to have a high probability of PAS should electively be delivered at such centers.

Ambulatory antenatal fetal electrocardiography in high-risk pregnancies (AMBER): protocol for a pilot prospective cohort study.

INTRODUCTION: Fetal heart rate (FHR) monitoring is a vital aspect of fetal well-being assessment, and the current method of computerised cardiotocography (cCTG) is limited to the hospital setting. Non-invasive fetal ECG (NIFECG) has the ability to produce FHR patterns through R wave detection while eliminating confusion with maternal heart rate, but is presently limited to research use. Femom is a novel wireless NIFECG device that is designed to be placed without professional assistance, while connecting to mobile applications. It has the ability to achieve home FHR monitoring thereby allowing more frequent monitoring, earlier detection of deterioration, while reducing hospital attendances. This study aims to assess the feasibility, reliability, and accuracy of femom (NIFECG) by comparing its outputs to cCTG monitoring. METHODS AND ANALYSIS: This is a single-centred, prospective pilot study, taking place in a tertiary maternity unit. Women with a singleton pregnancy over 28+0 weeks' gestation who require antenatal cCTG monitoring for any clinical indication are eligible for recruitment. Concurrent NIFECG and cCTG monitoring will take place for up to 60 min. NIFECG signals will be postprocessed to produce FHR outputs such as baseline FHR and short-term variation (STV). Signal acceptance criteria is set as <50% of signal loss for the trace duration. Correlation, precision and accuracy studies will be performed to compare the STV and baseline FHR values produced by both devices. The impact of maternal and fetal characteristics on the effectiveness of both devices will be investigated. Other non-invasive electrophysiological assessment parameters will be assessed for its correlation with the STV, ultrasound assessments and maternal and fetal risk factors. ETHICS AND DISSEMINATION: Approval has been obtained from South-East Scotland Research Ethics Committee 02 and MHRA. The results of this study will be published in peer-reviewed journals, and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT04941534.

Geographic variation in management of patients with placenta accreta spectrum: An international survey of experts (GPASS).

OBJECTIVE: To describe global geographic variations in the diagnosis and management of placenta accreta spectrum (PAS). METHODS: An international cross-sectional study was conducted among PAS experts practicing at medical institutions in member states of the United Nations. Survey questions focused on diagnostic evaluation and management strategies for PAS. RESULTS: A total of 134 centers participated. Participating centers represented each of the United Nations' designated regions. Of those, 118 (88%) reported practicing in a medium-volume or high-volume center. First-trimester PAS screen was reported in 35 (26.1%) centers. Respondents consistently implement guideline-supported care practices, including utilization of ultrasound as the primary diagnostic modality (134, 100%) and implementation of multidisciplinary care teams (115, 85.8%). Less than 10% of respondents reported routinely managing PAS without hysterectomy; these centers were predominantly located in Europe and Africa. Antepartum management and availability of mental health support for PAS patients varied widely. CONCLUSION: Worldwide, there is a strong adherence to PAS care guidelines; however, regional variations do exist. Comparing variations in care to outcomes will provide insight into the clinically significant practice variability.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.